% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{VzquezGarca:307369,
author = {C. Vázquez García and B. Obermayer and B. Keller and M.
Lebedin and C. Ratswohl and H. Abolhassani and A. Busse$^*$
and M. Di Virgilio and S. Mathas and D. Speiser and D. Beule
and Q. Pan-Hammarström and K. Warnatz and K. de la Rosa},
title = {{R}ecombination junctions from antibody isotype switching
classify immune and {DNA} repair dysfunction.},
journal = {Nature Communications},
volume = {nn},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DKFZ-2025-03013},
pages = {nn},
year = {2025},
note = {epub},
abstract = {Personalized assessment of immunocompetence and DNA
double-strand break (DSB) repair requires methods that are
sensitive to genetic and molecular complexity beyond the
well-known monogenic disorders. Inspired by decades of
research using B cells to study DNA repair processes, here
we present SWIBRID (SWItch junction Breakpoint Repertoire
IDentification), a tool to systematically profile genomic
junctions generated in vivo during antibody class switch
recombination (CSR) in B cells. As CSR junctions reflect
immune diversity and DNA repair proficiency, SWIBRID detects
phenotypic manifestations of deficiencies via a highly
scalable, blood-based PCR followed by long-read sequencing
and bioinformatic analysis. We show that specific DNA repair
defects, including cancer-associated mutations, exhibit
distinct CSR junction patterns. Notably, SWIBRID
distinguishes different types of DSB repair knockouts and
identifies the respective genetic defect in cell lines. In
68 patients, we detect immunodeficiencies and DNA repair
defects with high accuracy (area under the curve 0.99 and
0.84, respectively), and identify previously uncharacterized
patient groups as well as patient-specific CSR junction
signatures. With SWIBRID, we seek to advance the
identification of pathogenic defects, support early
diagnosis, and address molecular heterogeneity that drives
variable clinical outcomes.},
cin = {BE01},
ddc = {500},
cid = {I:(DE-He78)BE01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41419734},
doi = {10.1038/s41467-025-67206-5},
url = {https://inrepo02.dkfz.de/record/307369},
}